DESCRIPTION: The advent of induced pluripotent stems cells (iPSCs) has created unprecedented access to primary cell types such as cardiomyocytes and neurons, which may lead to the next-generation of drugs, regenerative medicine, and cancer treatments. Unfortunately, the iPS transformation and differentiation process produces a heterogeneous mixture of cell types, required cell sorting and purification for testing or therapy. For these electrically active cells it is critical to directly test their electrophysiological and functional behavior, yet current patch-clamping measurements are destructive, preventing further cell use, and non-contact methods do not have sufficient resolution to discriminate between different phenotypes. The field is thus limited to non-functional analysis techniques such as morphology or cell-surface markers as proxies. Here we propose a new method for non-contact electrical assessment: Single Cell Stethoscopes for measuring the acoustic waves given off by the cell when an action potential fires. While small, these pressure waves are measureable with ultra-sensitive hydrophones. Under this program, we will directly correlate the measured acoustic signals to patch clamp electrophysiology, and demonstrate the ability to identify individual cardiomyocyte cell types. These hydrophones will be an order of magnitude more sensitive than any existing at the relevant frequency ranges for cardiomyocytes (5-10 Hz), enabling measurements down to individual cells. We will further reveal the correlation between the electronic action potential and acoustic signals, and use these to non-destructively categorize and iPSC derived cardiomyocytes. These cell populations will be tested and benchmarked against known cell types, and the accuracy of the technique quantitatively assessed. This completed technology will dramatically impact the effectiveness and safety of iPSC-derived cells for disease modeling, regenerative medicine, and drug discovery.